Engineering 3D functional tissue constructs using self-assembling cell-laden microniches

Xing, Dan; Liu, Wei; Li, Jiao Jiao; Liu, Longwei; Guo, Anqi; Wang, Bin; Yu, Hongsheng; Yu, Zhiwen; Chen, Yuling; You, Zhifeng; Lyu, Cheng; Li, Wenjing; Liu, Aifeng; Du, Yanan; Lin, Jianhao

doi:10.1016/j.actbio.2020.07.058

Cited by 37 publications

(30 citation statements)

References 57 publications

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“…Chondrocytes (1 × 10 5 cells/cm 2 ) were grown in monolayer on 6-well plates (Corning/Costar 3516, USA), while MSCs (1 × 10 6 cells/cm 2 ) were grown on 6-well hanging inserts (Millicell, pore size 0.4 μm, Germany) under liquid-covered conditions, either as a monolayer (2D group) or within microniches (3D group). MSC-laden microniches in the 3D group were added to the co-culture system 2 h after the MSCs were seeded within microcarriers to allow cell adhesion [ 28 , 30 ]. The co-cultures were cultivated at 37 °C and 5% CO 2 for 7 days, in DMEM medium containing 10% (v/v) FBS and 1% (v/v) P/S.…”

Section: Methodsmentioning

confidence: 99%

“…When loaded with cells, these microcarriers form microniches that allow local accumulation of ECM and cell-cell interactions [ 29 ]. When packed into a geometrically confined 3D environment, the microniches may further self-assemble into functional 3D constructs [ 30 ]. We have shown that these injectable 3D microniches can increase the efficiency of cell therapy, whereby a low cell dose delivered within microniches can achieve similar effects as a high cell dose delivered directly in rat models of knee OA [ 31 ] and critical limb ischemia [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

Wang

Liu²,

et al. 2022

Bioactive Materials

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Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament (ACL) transection model of OA achieved similar reparative effects as repeated high doses of MSCs, as evaluated through imaging and histological analyses. Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer, together with MSCs grown either within 3D constructs or as a monolayer. Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group. RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group, as well as phenotypic maintenance in the co-cultured chondrocytes. The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

Wang

Liu²,

et al. 2022

Bioactive Materials

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“…As exemplified, the self-assembly of MSC-laden microniches within gelatin structures was employed to produce macroscale tissue constructs. 119 Here, the increase in cell-cell or cell-ECM interactions allowed for the selfassembly of the microniches. This self-assembly method is a potential solution to persisting problems in TE relating to cytotoxicity caused by traditional crosslinking methods and the problem of the loss of MSC's functional phenotype.…”

Section: Self-assemblymentioning

confidence: 98%

Advances in microfabrication technologies in tissue engineering and regenerative medicine

et al. 2022

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Background Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close‐to‐native three‐dimensional structures at numerous physiological scales, which are essential to confer the functional characteristics of living tissues. Methods In this article, we review a variety of microfabrication technologies that are currently utilized for several tissue engineering applications, such as soft lithography, microneedles, templated and self‐assembly of microstructures, microfluidics, fiber spinning, and bioprinting. Results These technologies have considerably helped us to precisely manipulate cells or cellular constructs for the fabrication of biomimetic tissues and organs. Although currently available tissues still lack some crucial functionalities, including vascular networks, innervation, and lymphatic system, microfabrication strategies are being proposed to overcome these issues. Moreover, the microfabrication techniques that have progressed to the preclinical stage are also discussed. Conclusions This article aims to highlight the advantages and drawbacks of each technique and areas of further research for a more comprehensive and evolving understanding of microfabrication techniques in terms of tissue engineering and regenerative medicine applications.

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“…Nanocarriers with a chondrocyte-specific aptamer have been widely used for sustained delivery in cartilage tissue, providing improved targeting specificity and pharmacokinetic profile (174)(175)(176). Tissue engineering can lead to the construction of a 'native' microenvironment to deliver drug/growth factors, maintain ECM deposition and support mechanical properties as naïve cartilage (177,178). This integration may form new approaches to the prevention and treatment of OA.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

G Protein-Coupled Receptors in Osteoarthritis

et al. 2022

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Osteoarthritis (OA) is the most common chronic joint disease characterized, for which there are no available therapies being able to modify the progression of OA and prevent long-term disability. Critical roles of G-protein coupled receptors (GPCRs) have been established in OA cartilage degeneration, subchondral bone sclerosis and chronic pain. In this review, we describe the pathophysiological processes targeted by GPCRs in OA, along with related preclinical model and/or clinical trial data. We review examples of GPCRs which may offer attractive therapeutic strategies for OA, including receptors for cannabinoids, hormones, prostaglandins, fatty acids, adenosines, chemokines, and discuss the main challenges for developing these therapies.

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Engineering 3D functional tissue constructs using self-assembling cell-laden microniches

Cited by 37 publications

References 57 publications

A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

Advances in microfabrication technologies in tissue engineering and regenerative medicine

G Protein-Coupled Receptors in Osteoarthritis

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